On May 23, 2019, the US-based chemical company BOC Sciences announces to upgrade its ADCs product line for cancer research as a targeted drug therapy. In addition to providing top quality ADCs that are GMP manufactured, BOC Sciences also provides custom synthesis service to develop antibody-drug conjugates based on individual needs for all phases of drug development.
ADCs consist of an antibody, a cytotoxic drug, and a linker that attaches the two. Being conjugated, they provide new insight into a broadly applicable method, which could increase the antitumor activity of antibodies and most importantly, improve the tumor-to-normal tissue selectivity of chemotherapy.
“An ideal ADC has a selective monoclonal antibody and a highly potent drug, mixed with properly stable linker (ADC Linker) systems via proper conjugation technologies that preserve the characteristics of the antibody. Theoretically, ADCs could be designed to target just any biological tumor target, as long as it can be reached by internalizing antibodies, “says Mr. Barron Jones, the Marketing Chief of BOC Sciences. “ADC is actually an innovative therapeutic application. Traditionally, monoclonal antibodies are tumor-specific but not very cytotoxic enough, small molecule drugs have good cell killing activity but are too toxic to be used on their own. So scientists decided to optimize the features of both components by linking them together.”
As to the how ADC works, Mr. Barron Jones further explains, “First, the monoclonal antibody are designed to bind to an antigen that is selectively expressed on the surface of a tumor cell. Upon binding, the antibody gets absorbed into the cell via receptormediated endocytosis, and then the antibody is trafficked to and degraded in the lysosome. Through this method, the cytotoxic agent (ADC Cytotoxin) could be directly delivered into the targeted cancer cell.”
However, in clinical trials, there are still many challenges facing ADCs. In brief, the choice of the cytotoxin and the exact nature of the connection to the antibody are critical for the success of this method. Moreover, the appropriate mAb format is best to be selected to tune ADC tumor uptake and take other factors into consideration, such as blood clearance properties, linker stability and drug release.
2019年5月23日，美国化学公司 BOC Sciences 宣布将其 ADC 肿瘤研究产品线升级为靶向药物治疗。除了提供高质量的 GMP 制造的 ADC 外， BOC Sciences 还提供定制的合成服务，根据药物开发各个阶段的个别需求开发抗体药物共轭物。
“理想的 ADC 具有选择性单克隆抗体和强效药物，通过保持抗体特性的合适的共轭技术与适当稳定的链接剂（ ADCLinker ）系统混合。BOC Sciences 的市场总监 Barron Jones 说，“从理论上讲， ADC 的设计可以只针对任何生物肿瘤目标，只要通过内化抗体就能达到。“ ADC 实际上是一种创新的治疗应用。传统上，单克隆抗体具有肿瘤特异性，但细胞毒性不够强，小分子药物具有良好的细胞杀伤活性，但毒性太强，不能单独使用。因此，科学家决定通过将这两个组件连接在一起来优化它们的特性。”
关于 ADC 的工作原理， Barron Jones 先生进一步解释说，“首先，单克隆抗体被设计成与肿瘤细胞表面选择性表达的抗原结合。结合后，抗体通过可再生的内吞被吸收到细胞中，然后抗体被运送到溶酶体中并降解。通过这种方法，细胞毒剂（ ADC Cytotoxin ）可以直接输送到目标癌细胞中。”
然而，在临床试验中， ADC 仍然面临许多挑战。总之，细胞毒素的选择和抗体连接的确切性质是该方法成功的关键。此外，最好选择合适的 mAb 格式来调整 ADC 肿瘤的摄取，并考虑血液清除率、连接器稳定性和药物释放等其他因素。